In vitro and in silico insights into tyrosinase inhibitors with (E)-benzylidene-1-indanone derivatives

Hee Jin Jung; Sang Gyun Noh; Yujin Park; Dongwan Kang; Pusoon Chun; Hae Young Chung; Hyung Ryong Moon

doi:10.1016/j.csbj.2019.07.017

In vitro and in silico insights into tyrosinase inhibitors with (E)-benzylidene-1-indanone derivatives

Comput Struct Biotechnol J. 2019 Aug 1:17:1255-1264. doi: 10.1016/j.csbj.2019.07.017. eCollection 2019.

Authors

Hee Jin Jung^{1

2

3}, Sang Gyun Noh^{1

2

3}, Yujin Park¹, Dongwan Kang¹, Pusoon Chun⁴, Hae Young Chung^{1

2

3}, Hyung Ryong Moon¹

Affiliations

¹ College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea.
² Longevity Life Science and Technology Institutes, Pusan National University, Busan 46241, Republic of Korea.
³ Aging Tissue Bank, College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea.
⁴ College of Pharmacy, Inje University, Gimhae 47392, Republic of Korea.

Abstract

Tyrosinase is a key enzyme responsible for melanin biosynthesis and is effective in protecting skin damage caused by ultraviolet radiation. As part of ongoing efforts to discover potent tyrosinase inhibitors, we systematically designed and synthesized thirteen (E)-benzylidene-1-indanone derivatives (BID1-13) and determined their inhibitory activities against tyrosinase. Among the compounds evaluated, BID3 was the most potent inhibitor of mushroom tyrosinase (IC₅₀ = 0.034 µM, monophenolase activity; IC₅₀ = 1.39 µM, diphenolase activity). Kinetic studies revealed that BID3 demonstrated a mixed type of tyrosinase inhibition with K _i value of 2.4 µM using l-DOPA as a substrate. In silico molecular docking simulations demonstrated that BID3 can bind to the catalytic and allosteric sites of tyrosinase to inhibit enzyme activity which confirmed in vitro experimental studies between BID3 and tyrosinase. Furthermore, melanin contents decreased and cellular tyrosinase activity was inhibited after BID3 treatment. These observations revealed that BID3 is a potent tyrosinase inhibitor and potentially could be used as a whitening agent for the treatment of pigmentation-related disorders.

Keywords: 1-Indanone; 2,4-Dihydroxy benzylidene; Melanin; Tyrosinase inhibitor.